MLT-748 is a potent, selective and allosteric inhibitor of MALT1 with IC50 of 5 nM, binding at the interface between the caspase and immunoglobulin (Ig3) domains by displacing Trp580 and locking the catalytic site in an inactive state.
MLT-748 binds MALT1 in the allosteric Trp580 pocket. MLT-748 binds and stabilizes mutant MALT1-W580S. Cleavage of MALT1 substrates is blocked by MLT-748 in B and T cells. MLT-748 rescues MALT1 function in patient MALT1mut/mut lymphocytes.[1]
[1] Quancard J, et al. Nat Chem Biol. 2019 Mar;15(3):304-313.
















